Calcium antagonist drugs, such as verapamil, have recently been shown to have some inhibitory effects on the development of atherosclerosis and of the smooth muscle hyperplasia in hypertension. Some of this has been attributed to decreases in blood pressure and to antiplatelet effects. Verapamil has also been shown to alter metabolism of low density lipoproteins. However, because calcium is a requirement for cell growth, which can be inhibited by lowering the extracellular calcium concentrations in vitro, studies have recently looked for direct inhibition of cell growth by calcium antagonists. Verapamil and nifedipine have been found to inhibit the growth of cultured vascular smooth muscles at 10-5 to 10-6 M but effects at physiologic range (10-7) were slight. Those studies were performed in the presence of 10% serum, using rapidly growing cells and cells made quiescent by starvation. We took another approach and studied cells made quiescent by starvation but refed with zero to 0.1% serum. We found a 6-fold increase in thymidine incorporation in these cells when given verapamil at low -8 to 10-7M. Inhibition was seen at 10-5M verapamil when cells were refed with 10% serum no effect was observed until 10-5M, at which point inhibition was seen as in the previous studies. This novel observation suggests two hypotheses: 1) that starved quiescent smooth muscle cells are deficient in ATP, cannot maintain the electrochemical calcium gradient and, because of calcium leakage into the cell, experience a form of calcium mediated growth inhibition which is preventable by verapamil; 2) there is a growth inhibitor signal in confluent starved cells which is mediated by calcium entry and this entry is through voltage dependent channels and hence prevented by verapamil.